Yang Honghong, Zhang Chunhong, Fang Shan, Ou Rongying, Li Wenfeng, Xu Yunsheng
Laboratory for Interdisciplinary Research, Institution for Translational Medicine, The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou, Zhejiang Province, China; Department of Dermatovenerology, The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou, Zhejiang Province, China.
Laboratory for Interdisciplinary Research, Institution for Translational Medicine, The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou, Zhejiang Province, China; Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou, Zhejiang Province, China.
Int J Clin Exp Pathol. 2015 Nov 1;8(11):13957-67. eCollection 2015.
Gastric cardiac adenocarcinoma (GCA) accounts for a majority of gastric cancer population and harbors unfavorable outcome. Ubiquitin C-terminal hydrolase L1 (UCH-L1) belongs to the deubiquitinating enzyme family, which could regulate cell growth in human cancers. In the present study, expression of UCH-L1 was evaluated in 196 GCAs by immunohistochemistry using tissue microarray and its function on gastric cancer cells was measured. UCH-L1 expression was increased in GCA specimens, compared with their normal tissues and UCH-L1 overexpression is tightly correlated with tumor size and overall TNM stage. Log-rank analysis showed that UCH-L1 positive is reversely associated with cumulative survival (P<0.001). Multivariate Cox regression model showed that UCH-L1 overexpression is a remarkably negative predictor in GCA prognosis (Hazard Ratio=0.53, P<0.01), along with advanced TNM stage that is a known negative factor in gastric cancers (Hazard Ratio=0.33, P<0.05). Silencing of UCH-L1 reduced the ability of cell proliferation, colony formation, migration and invasion of gastric cancer cells. Our findings suggest that UCH-L1 is a promising prognostic biomarker for GCAs and might play an important role in the carcinogenesis of gastric cancer.
贲门胃腺癌(GCA)占胃癌患者的大多数,且预后不良。泛素C末端水解酶L1(UCH-L1)属于去泛素化酶家族,可调节人类癌症中的细胞生长。在本研究中,使用组织芯片通过免疫组织化学评估了196例GCA中UCH-L1的表达,并检测了其对胃癌细胞的作用。与正常组织相比,GCA标本中UCH-L1表达增加,且UCH-L1过表达与肿瘤大小和总体TNM分期密切相关。对数秩分析显示,UCH-L1阳性与累积生存率呈负相关(P<0.001)。多变量Cox回归模型显示,UCH-L1过表达是GCA预后的显著负性预测因子(风险比=0.53,P<0.01),同时TNM分期进展也是胃癌已知的负性因素(风险比=0.33,P<0.05)。沉默UCH-L1可降低胃癌细胞的增殖、集落形成、迁移和侵袭能力。我们的研究结果表明,UCH-L1是GCA有前景的预后生物标志物,可能在胃癌的致癌过程中起重要作用。